As our understanding of the innervation of the urinary bladder increases, it is evident that this innervation is very complex. Cholinergic, adrenergic and purinergic nerve fibers innervate the bladder and its related structures, the urethra and the ureters. No longer does it seem true that micturition is simply due to cholinergic excitation of the bladder accompanied by adrenergic inhibition of the bladder. ATP, other purinergic analogs, and perhaps peptidergic agents, such as Substance P, are apparently involved in the fine control mechanisms which monitor collection, retention and elimination of urine. The proposed studies are designed to determine the involvement of purinergic agents in the physiological control of the lower urinary tract, specifically the closure of the internal urethral sphincter and/or the pelvic-nerve evoked urinary bladder contractions. In addition, the studies will determine if there are ureterovesical interactions influencing ureteral peristalsis and which can be altered pharmacologically. Substance P, ATP and other purinergic and peptidergic agents will be used to alter ureteral peristalsis, and to investigate any ureterovesical interaction. Electron microscopy will be used to examine pelvic ganglionic tissue after 6-hydroxy-dopamine pretreatment or surgical sympathectomy of the bladder. This phase of the project is designed to provide direct physical evidence for the origin of purinergic nerves which seem to innervate the urinary bladder.